Division of Infectious Diseases, Department of Internal Medicine, University of Texas Medical School, Houston, Texas, USA.
PLoS Pathog. 2010 Jan 8;6(1):e1000716. doi: 10.1371/journal.ppat.1000716.
Ace is an adhesin to collagen from Enterococcus faecalis expressed conditionally after growth in serum or in the presence of collagen. Here, we generated an ace deletion mutant and showed that it was significantly attenuated versus wild-type OG1RF in a mixed infection rat endocarditis model (P<0.0001), while no differences were observed in a peritonitis model. Complemented OG1RFDeltaace (pAT392::ace) enhanced early (4 h) heart valve colonization versus OG1RFDeltaace (pAT392) (P = 0.0418), suggesting that Ace expression is important for early attachment. By flow cytometry using specific anti-recombinant Ace (rAce) immunoglobulins (Igs), we showed in vivo expression of Ace by OG1RF cells obtained directly from infected vegetations, consistent with our previous finding of anti-Ace antibodies in E. faecalis endocarditis patient sera. Finally, rats actively immunized against rAce were less susceptible to infection by OG1RF than non-immunized (P = 0.0004) or sham-immunized (P = 0.0475) by CFU counts. Similarly, animals given specific anti-rAce Igs were less likely to develop E. faecalis endocarditis (P = 0.0001) and showed fewer CFU in vegetations (P = 0.0146). In conclusion, we have shown for the first time that Ace is involved in pathogenesis of, and is useful for protection against, E. faecalis experimental endocarditis.
Ace 是一种黏附素，可与肠球菌属粪肠球菌在血清中或存在胶原蛋白的情况下生长条件下表达的胶原蛋白结合。在这里，我们生成了一个 ace 缺失突变体，并表明其在混合感染大鼠心内膜炎模型中相对于野生型 OG1RF 显著减弱（P<0.0001），而在腹膜炎模型中则没有观察到差异。OG1RFDeltaace（pAT392::ace）的互补菌株（pAT392::ace）与 OG1RFDeltaace（pAT392）相比，在早期（4 小时）心脏瓣膜定植方面增强（P = 0.0418），表明 Ace 表达对于早期附着很重要。通过使用特异性抗重组 Ace（rAce）免疫球蛋白（Ig）的流式细胞术，我们在体内直接从感染性植物中获得的 OG1RF 细胞中显示 Ace 的表达，这与我们之前在粪肠球菌心内膜炎患者血清中发现抗 Ace 抗体的发现一致。最后，主动针对 rAce 免疫的大鼠比未免疫（P = 0.0004）或假免疫（P = 0.0475）大鼠对 OG1RF 的感染敏感性降低。同样，给予特异性抗 rAce Ig 的动物发生粪肠球菌实验性心内膜炎的可能性较低（P = 0.0001），并且植物中的 CFU 较少（P = 0.0146）。总之，我们首次表明 Ace 参与了粪肠球菌实验性心内膜炎的发病机制，并可用于保护其免受感染。
